Hanzhang Lu, Ph.D.

Hanzhang Lu
Hanzhang Lu, Ph.D.

Hanzhang Lu, Ph.D., concentrates on developing MRI techniques to understand brain function, including the regulation of blood supply, the mechanism of the fMRI signal, functional connections among brain regions, and neuroplasticity, or how neurons adjust the strength of their interconnections in learning. His research aims at improving understanding, diagnosis, and treatment of brain disorders including neurodegenerative diseases, schizophrenia, and cerebral vascular diseases. (For more information, see Lu laboratory website.)

His strategies include developing and applying novel pulse sequences that make the MR signal sensitive to different physiological parameters of the brain. For example, one technique he uses is arterial spin labeling. This method involves using a specialized series of radio frequency (RF) pulses and magnetic field gradients to generate a pulse sequence that labels the incoming blood flow in a specific brain region. This magnetic label consists of inverting the spin of hydrogen atoms in water molecules in blood flowing into the brain. Researchers can use this labeling to determine the extent of blood flow into a specific region by detecting whether the signal from this labeled blood appears in the region. Since blood flow reflects a region's requirements for oxygenated blood due to higher activity, such measurements offer insights into brain activity in the region. For example, Dr. Lu is using arterial spin labeling to analyze neural function in brain regions involved in schizophrenia, seeking clues to the mechanism of the disease.

Dr. Lu is also using arterial spin labeling to measure elasticity of blood vessels in the brain. In these experiments, subjects whose brains are being scanned are asked to inhale air containing higher-than-normal levels of carbon dioxide, which causes the blood vessels in the brain to dilate. By detecting the extent of this dilation, MRI scans can measure vessel elasticity. Such elasticity measurements could identify people at risk of transient ischemic attack or stroke. Also, Dr. Lu is conducting vessel elasticity studies in people with Alzheimer's disease to understand its role in the disease.

Diminished elasticity in blood vessel could be the cause of some cognitive deficits in the elderly. This inelasticity could compromise mental function by preventing neural regions from reacting to new activity by increasing blood supply. Although the mechanism of this "vascular dementia" is different from that of Alzheimer's disease, in which brain cells are killed by accumulations of abnormal proteins, the two pathologies are extremely difficult to distinguish from one another.

The vast majority of MRI studies have been done on the brain's grey matter, the major component of the central nervous system, because it is easily imaged due to extensive blood circulation. However, Dr. Lu is developing high-sensitivity MRI techniques to image blood flow in the brain's white matter, which consists mainly of nerve cells encased in an insulating fatty myelin sheath. White matter has far fewer blood vessels, making it relatively invisible on MRI scans. The ability to image blood flow in white matter would give greater insight into brain function in both normal and diseased brains.

Dr. Lu is also seeking to develop the first noninvasive method of measuring neuroplasticity. He is attempting to identify telltale markers of plasticity detectable in MRI scans that would enable researchers to map rewiring of the brain in real time during learning in humans. Until now, such studies of the mechanisms of learning have been done in isolated brain cells in culture, or in animals using implanted measuring electrodes. The ability to map neuroplasticity in real time would not only enable better understanding of normal brain function in learning, but of the effects of neurodegenerative disease such as Alzheimer's disease. Also, studying the effects of stroke on neuroplasticity could contribute to improved therapies for stroke recovery.

A major problem in using functional MRI for clinical diagnosis and research is the large variation in the blood oxygen-level dependent (BOLD) signal from person to person. This signal can double from one person to another, and researchers currently do not understand the basis for this difference. Dr. Lu is working to understand the physiological basis of these intersubject differences, to establish baseline criteria for such measurements. These criteria would enable clinicians and researchers to correct for such variations, enabling more precise identification of brain abnormalities. Another measurement problem is intrasubject variation, in which BOLD signals can change over time in the same subject. Dr. Lu is also working to understand the basis of such variation, so researchers and clinicians can correct for it.

For publication information please view Dr. Lu's faculty profile.